The proposed research is designed to identify optimal cessation intervention components across three phases of the cessation process: Precessation, Pericessation, and Maintenance. Project 1 comprises two experiments that are based on the Center-wide intervention optimization approach that relies upon factorial designs and sequential experiments to efficiently engineer and evaluate interventions (Collins et al., 2005, 2007). The specific aim of Experiment 1 a is to determine the optimal intervention strategies to use in the first 2 weeks following the quit day (the Pericessation Phase). Three factors will be tested in a factorial design: varenicline vs. placebo pill; clinician cessation counseling (minimal vs. intensive); and phone counseling (minimal vs. intensive). Experiment 1 a will determine which combination of these components produces optimal effects on measures of mechanism and outcome. The placebo pill condition allows for the demonstration of varenicline efficacy and permits the examination of intervention mechanisms. The specific aim of Experiment 1b is to examine Precessation and Maintenance Phase (postquit week 3 to 6 months) interventions, when used in combination with the optimal Pericessation strategy identified from Experiment 1a. Four factors will be tested in a factorial design: extended (3 weeks) Precessation varenicline vs. standard 1 week of Precessation varenicline; enhanced Precessation counseling (3 sessions) vs. minimal Precessation counseling (one session); extended Maintenance use of varenicline (25 weeks) vs. standard 13 weeks of varenicline; and extended counseling (5 phone sessions) vs. no additional counseling. Experiment 1 b will determine which of these Precessation and Maintenance intervention components produce optimal effects on measures of mechanism and outcome. The ultimate goal of this research is to engineer an optimal, comprehensive smoking cessation intervention package. The best Precessation, Pericessation and Maintenance intervention components will be selected based upon an appraisal of statistical significance, effect size, cost-effectiveness and other evaluative criteria.